PROJECT SUMMARY Over the last twenty years, training in Physiology departments throughout the country has undergone a transformation that creates a challenge for students seeking an understanding of the discipline at the whole animal to the cellular and molecular levels. One exception is the Physiology Department of the Medical College of Wisconsin (MCW), that offers exceptional research training emphasizing the integration of knowledge at all of these levels, and the relationship of this knowledge to human disease processes. In our current proposal, we will continue providing this outstanding training in cellular, molecular, and whole animal Physiology for 6 NIH- supported trainees each year. In addition, we request funds to provide stipends for 6 rising 2nd year medical students enrolled at MCW to spend 11 weeks during the summer engaged in research in the laboratory of one of our faculty to enhance recruitment of medical students into biomedical research. Unique aspects of the proposed PhD training are the multidisciplinary mentoring program and opportunities for translational research fostered by a highly collaborative basic science and clinical faculty. Graduate students will be recruited nationally and selected for admission on the basis of undergraduate academic credentials, previous research experience, and commitment to a career in research. Students must successfully complete the requirements of the first two years of graduate school before being considered for T32 support. Selection of T32 trainees will be based on performance in course work, the preliminary examination and in research. Trainees are full-time Ph.D. candidates in the MCW Graduate School, and will complete a research that includes use of the techniques in molecular, cellular, tissue, and whole-animal or clinical investigation. Research training is supervised by Physiology faculty along with co-mentors from other basic science and clinical departments. Trainees will undergo continuous evaluation by utilizing Individual Development Plans created upon matriculation, which are reviewed and updated yearly. The major objective is to provide trainees with a broad foundation in interdisciplinary basic science and translational research through developing critical thinking, integrative reasoning, and technical skills required to succeed in evolving research careers focused on the prevention of hypertension, stroke, and respiratory diseases. An innovative feature of the training is the emphasis on addressing the national need to train for the integrated- systems approaches that represent the future of biomedical research in the post-genomic era. The success of our program in research is indicated by the 47 first-authored publications from 24 T32 supported graduates over the past 10 years (Table 5A), and their contribution to 51 manuscripts coauthored with other students or faculty, indicative of our highly collaborative training program. Another measure of overall success of our program is that 94% of T32 trainees who completed our program over the past 15 years (Table 8A) have continued in a biomedical field, with 18 obtaining research, teaching, and/or patient care faculty positions and only two trainees withdrew from the program without obtaining the PhD (average duration of training was 4.96 years).